An NMR major users group consisting of 5 NIH-funded investigators and 9 minor users with NIH or NSF funding is applying for funds for the purchase of a Bruker or Varian 600 MHz NMR spectrometer console equipped with a triple resonance cryogenic probe. The requested console will replace, at Johns Hopkins School of Medicine (SOM) NMR facility, an 18 year old console which recently suffered a catastrophic failure and has been decommissioned. There is currently no operational high-field spectrometer at the SOM, and the research programs of the user base have been significantly impaired. Although the users have access to other spectrometers located at the Arts and Science campus, these machines are now constantly utilized with significant waiting times for data acquisition that are now slowing down research investigations. The users are located across six Departments and three Schools of the Johns Hopkins University (JHU) and the requested instrument will be used to advance fundamental research into the structure, mechanism and dynamics of biological macromolecules using multi-dimensional heteronuclear NMR methods. This instrumentation will impact a wide range of health related basic research projects in the areas of DNA repair, protein-DNA interactions, protein stability, molecular mechanisms of carcinogenesis, protein folding diseases, protein degradation pathways and signal transduction mechanisms. This acquisition will restore the NMR facility at Hopkins School of Medicine to a state-of-the-art level, and will allow these research programs to take advantage of magnet and probe technologies that are essential for studying large biological molecules under dilute conditions. The new system will provide the chemical shift dispersion and sensitivity that is essential for studying denatured states of proteins, aliphatic proton regions of nucleic acids, and obtaining spectral resolution of native 20-40 kDa proteins and large protein-DNA complexes that are now under study. In addition, NMR data will be acquired with sensitivity that will be at least 1.7-fold greater than the current 600 MHz instrument, enhancing the study of biological molecules that are challenging due to inherent weakness of the NMR signals, low solubility, low sample availability, or short-lived stability. This acquisition will rescue oversubscription of the Hopkins NMR facilities on both campuses arising from two recent NMR faculty recruitments and also several new research projects that extensively utilize the instruments at the facility. PUBLIC HEALTH RELEVANCE: Funds are requested to obtain a replacement 600 MHz NMR spectrometer console and cryoprobe system that will be used for health related structural and mechanistic research in the areas of enzymatic DNA repair, protein-nucleic acid interactions, molecular mechanisms of carcinogenesis, protein folding diseases, protein degradation pathways and signal transduction mechanisms.